The central goal of this proposal is to develop and implement a genotyping strategy for the human genome which permits high throughput genotyping to be achieved at low cost and high efficiency. We have developed an approach based on interspersed repeat sequence per (IRS PCR) which successfully addresses these objectives in the mouse. In this proposal, I propose to develop and implement a related strategy for human genotyping based on the experience we have gained in the development of low cost, high throughput genotyping in the mouse. The adaptation of an IRS PCR based approach to human genotyping will require significant development work. The goals of this proposal are therefore: 1. To carry out the development work necessary to establish an optimal path or paths for implementation of an IRS PCR based strategy for human genotyping. Alternative approaches and strategies will be critically tested and evaluated during this analytical phase of the project. 2. Once optimal strategies are established for identifying and scoring polymorphic markers we propose to implement a genome wide development of genetic markers appropriate for genotyping by the IRS PCR based strategy to support rapid, low cost genotyping of human DNA. 3. The long term goal of the proposal will be to develop a very high marker density which will effectively support complex trait analysis as well as linkage studies for traits which segregate in a simple Mendelian pattern.